Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

A Significance of an Amelioration of Endothelial Dysfunction by Sodium-Glucose Cotransporter 2 Inhibitors for an Improvement of Heart Failure and Chronic Kidney Disease

Version 1 : Received: 20 April 2023 / Approved: 2 May 2023 / Online: 2 May 2023 (02:18:51 CEST)

A peer-reviewed article of this Preprint also exists.

Yanai, H.; Adachi, H.; Hakoshima, M.; Katsuyama, H. Significance of Endothelial Dysfunction Amelioration for Sodium–Glucose Cotransporter 2 Inhibitor-Induced Improvements in Heart Failure and Chronic Kidney Disease in Diabetic Patients. Metabolites 2023, 13, 736. Yanai, H.; Adachi, H.; Hakoshima, M.; Katsuyama, H. Significance of Endothelial Dysfunction Amelioration for Sodium–Glucose Cotransporter 2 Inhibitor-Induced Improvements in Heart Failure and Chronic Kidney Disease in Diabetic Patients. Metabolites 2023, 13, 736.

Abstract

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

Keywords

endothelial dysfunction; chronic kidney disease; heart failure; sodium-glucose cotransporter 2 inhibitors

Subject

Biology and Life Sciences, Endocrinology and Metabolism

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